Studies on Dihydropyridines. III.1) Synthesis of 4,7-Dihydrothieno[2,3-b]-pyridines with Vasodilator and Antihypertensive Activities

Abstract

A series of 4-aryl-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate derivatives (I) was synthesized and tested for binding affinity to Ca2+ channels in rat cerebral cortex membranes, coronary vasodilator effect in isolated guinea pig hearts, and antihypertensive activity in spontaneously hypertensive rats. Several compounds had potent coronary vasodilator and antihypertensive activities. The structure-activity relationships of the series indicated that a lipophilic 3-alkyl substituent with moderate bulkiness was effective for enhancing the pharmacological potencies. Among them, methyl 4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2,3-b]-pyridine-5-carboxylate (S-312) was selected as a promising cardiovascular agent. The relationship between the absolute configuration of S-312 and its biological activities is also presented. © 1988, The Pharmaceutical Society of Japan. All rights reserved.